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Flashcards in Folic acid inhibitor Deck (47):
1

The 2 enzyme target for bacterial folate antagonists are

Dihydropteroate synthetase (sulfonamides; competes with PABA)
Dihydrofolate reductase (trimethoprim)

2

structural analogs of PABA and competitively inhibit the enzyme dihydropteroate synthase

Sulfonamide drugs

3

bacteriostatic against gram (+) and gram (-) bacteria

Sulfonamides

4

What are the 3 groups of sulfonamides?

1) Oral absorbable: Sulfadiazine, Sulfisoxazole, Sulfamethoxazole ( + trimethoprim)
2) Oral nonabsorbable agents: Sulfasalazine
3) Topical agents: Sodium sulfacetamide (Sulamyd), Silver sulfadiazine (Silvadene)

5

Sulfadiazine

An oral absorbable sulfonamide.
Used for: UTI; nocardiosis, rheumatic fever; prophylaxis; toxoplasmosis; uncomplicated malaria

6

Sulfamethoxazole ( + trimethoprim)

An oral absorbable sulfonamide
Used for: URI; UTI; prophylaxis and tx of P. carinii

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Sulfisoxazole

An oral absorbable sulfonamide
Used for: Otitis media; UTI; chloroquine-resistant malaria
drug resistant malaria and Toxoplasma gondii

8

Sulfasalazine

Oral nonabsorbable sulfonamide
Used for UC, enteritis
Delayed –release tablets used to treat RA
Anti-inflammatory properties due to cleavage of sulfasalazine to sulfapyridine and 5-aminosalicylate

9

Sodium sulfacetamide (Sulamyd)

Topical sulfonamide. Used in ophthalmic solution or ointment for bacterial conjunctivitis
Also used to treat chlamydia trachoma infections most common cause of preventable blindness worldwide

10

Silver sulfadiazine (Silvadene)

Topical sulfonamide. Topical for burn infection prophylaxis

11

Sulfonamides: distrubution

Distributed throughout body including CNS and fetus
Sulfamethoxazole is highly protein bound to albumin (if you have a drug that’s highly bound to albumin, may displace)
Protein binding drug interactions (narrow therapeutic index to these meds): Warfarin, phenytoin, sulfonylureas

12

Sulfonamides: Adverse Effects

N/V/D, HA, photosensitivity
Fever
Skin rashes- Mild to life threatening
Blood dyscrasias including hemolytic anemia
Numerous “itis’s” (nephritis, hepatitis, vasculitis)
Crystalluria

13

Competitive inhibitor of dihydrofolic acid reductase
converts dihydrofolic acid to tetrahydrofolic acid
The next step in purine synthesis
Resistance also common

Trimethoprim

14

Trimethoprim: adverse effects

1) GI
2) megaloblastic anemia, leukopenia, granulocytopenia reversed with folinic acid

15

Uses for trimethoprim

Can be used alone for community acquired UTI or for prophylaxis of UTI

16

Combination of Trimethoprim+sulfamethoxazole is bactericidal or -static?

Bactericidal.
(whereas sulfamethoxazole on its own is -static)

17

What is the only Only available IV sulfonamide antibiotic

Trimethoprim+sulfamethoxazole (Bactrim/Septra)

18

Uses for Trimethoprim+sulfamethoxazole (Bactrim/Septra)

Alternative agent for: Community acquired pneumonia, UTI and prostatitis, Acute otitis media (not first choice unless you have PCN allergy)
Treatment of pneumocystis carinii (HIV pts)
Bacterial diarrhea
Prophylaxis: UTI, PCP & Toxoplasma gondii in AIDS pts, Peritonitis prevention in pts with cirrhosis

19

Drug that Inhibits DNA processing by:
Inhibition of DNA topoisomerases

Quinolones (fluoroquinolones)

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Drugs that Inhibit DNA processing by: Inhibition of DNA-dependent RNA polymerase

Directly - rifampin
Indirectly - nitrofurantoin

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Name this drug based on action: Block bacterial DNA synthesis by inhibiting DNA topoisomerase IV and topoisomerase II (DNA gyrase)
Inhibit DNA supercoiling, transcription and repair

Quinolones

22

Quinolones act against which bacteria?

Active against gram (+) and gram (-) bacteria
Activity against Topo IV accounts for gram (+) spectrum

23

Primary target of quinolones differ according to what?

according to organism.
Topo II primary, Topo IV secondary
E.coli
Topo IV primary, Topo II secondary
Staphylococci, streptococci

24

Spectrum of activity of quinolones

Originally developed for enhanced gram negative coverage
Campylobacter, Enterobacter, E. coli, H. influenzae, Klebsiella, Salmonella typhi, Shigella, Vibrio cholerae
Limited activity against gram positive organisms

25

Ciprofloxacin (Cipro)

quinolone. Excellent gram negative coverage with only moderate gram positive activity

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Levofloxacin (Levaquin)
Moxifloxacin (Avelox)

quinolones. Excellent gram negative coverage with improved gram positive coverage

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Trovafloxacin (Trovan)

quinolone. Continued gram negative and gram positive coverage with enhanced anaerobic coverage (B. Fragilis)

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List quinolones

Ciprofloxacin (Cipro)
Levofloxacin (Levaquin)
Moxifloxacin (Avelox)
Trovafloxacin (Trovan)

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Atypical pneumonia organisms that quinolones work against

Chlamydia pneumoniae
Mycoplasma pneumoniae

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intracellular pathogens that quinolones work against

Legionella
Mycobacteria tuberculosis
Mycobacteria avium complex

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clinical uses of quinolones

UTI
Sinusitis
Mycobacterial infections
Bacterial diarrhea
Salmonella, shigella, vibrio, campylobacter, traveler’s diarrhea
Soft tissue, bone and joint infections
Decubitis, prosthetic joints, osteomyelitis
Gonococcal and chlamydial infections
Pneumonia (community- or hospital-acquired)
Post-exposure prophylaxis for anthrax = cipro
Tx inhalation anthrax infection = levofloxacin
Trovafloxacin FDA restricted to life- or limb-threatening infections
Severe hepatic toxicity

32

Gatifloxacin, levofloxacin, lomefloxacin and ofloxacin eliminated by?

Renal excretion

33

Trovafloxacin and moxifloxacin are excreted?

non-renally (bile)

34

Drug interactions of quinolones

Antacids, sucralfate, iron, multivitamins
CYP interactions most common with ciprofloxacin
Methadone and theophylline levels increased
Severe, fatal hypoglycemia with concurrent use of glyburide (diabetic pts)

35

Moxifloxacin (Avelox)

quinolone. Oral or IV; broad spectrum single daily dose; targets DNA gyrase instead of Topo IV in gram (+)

36

Gemifloxacin (Factive)

quinolone. Approved to treat mild-moderte CAP due to multi-drug resistant Streptococcus pneumoniae

37

Metronidazole (Flagyl): MOA

Bactericidal
Metabolized to an intermediate that inhibits bacterial DNA synthesis and degrades existing DNA.
Selectivity due to its toxic metabolite that is not produced in mammalian cells

38

Metronidazole (Flagyl): spectrum of activity

Anaerobic and protozoan infections
Amebiasis; trichomoniasis; skin infections; CNS infections; intra-abdominal infections; systemic anaerobic infections; tx C. dif; bacterial vaginosis; H. pylori; acne rosacea

39

Metronidazole (Flagyl): contraindications

History of blood dyscrasias
History of alcoholism
Hepatic disease
CNS disorders
Visual changes
1st trimester of pregnancy- disrupts organ formation-fatal (Category B in 2nd and 3rd trimester)

40

Metronidazole (Flagyl): Drug interactions

Warfarin -->increased INR (international normalized ratio—how long it takes blood to clot. Increasing this= more likely to bleed)
Cimetidine (p450 inhibitor)  increased metronidazole levels
Lithium toxicity (bipolar conditions)
ETOH disulfiram-like rxn (flushing, HA, N/V, sweating or tachycardia

41

Metronidazole (Flagyl): ADRs

Vertigo, HA, confusion, seizures
Edema
N/V/D, abdominal cramping, constipation
Darkened urine, polyuria, dysuria,
Transient leukopenia, neutropenia (reversible)

42

Nitrofurantoin (Macrodantin, Macrobid): MOA

Poorly defined; appears to require reduction for activity --> reactive forms damage DNA and interfere with RNA synthesis and DNA replication
Bacteriostatic-low conc.
Bactericidal-high
Spectrum: Gram (+) & Gram (-)

43

Nitrofurantoin (Macrodantin, Macrobid): ADRs

GI: N/V
Interstitial pulmonary fibrosis with chronic use
Hemolysis in patients with G6PD deficiency
Aggranulocytosis, thrombocytopenia (reversible)
Peripheral neuropathies, HA, dizziness
Significant skin reactions w/allergies.

44

Polymyxin B: MOA

Bactericidal
Interact w/phospholipids on the outer plasma cell membranes of gram (-) bacteria, disrupting their structure.
Disruption destroys bacteria’s osmotic barrier leading to lysis

45

What bacteria does Polymyxin B work against?

Gram (-) bacteria
Pseudomonas aeruginosa

46

Daptomycin (Cubicin): indications

Reserve. Used for multi-drug resistant gram (+) bacteria
Bactericidal disruption of plasma membrane function by acyl tail poking hole in membrane allowing depolarization doesn’t penetrate into cytopolasm

47

Daptomycin (Cubicin): ADRs

reversible myopathy, GI (N/V/D)